What factors should be considered when making treatment recommendations for this patient?
Treatment for anovulation is guided by the goals of therapy. Since anovulation is an endocrine abnormality, medical treatment is first line [31].If secondary causes are diagnosed, these should be treated first. Other goals of treatment can include reducing amount and irregularity of menstruation, provide contraception, increasing ovulation in women with desired fertility, and reducing androgenic sequelae such as acne and hirsutism.
When treating the irregular or heavy bleeding associated with anovulation, first-line treatment is exogenous hormone. This can be in the form of combined estrogen/progesterone formulations (pill, patch, and ring). Medroxyprogesterone (medroxyprogesterone acetate 5–10 mg daily) taken 10 to 14 days per month is another option. Standard consideration for medical eligibility in prescribing these agents should be considered (see U.S. medical eligibility criteria for contraceptive use available at www.cdc.gov/reproductivehealth/unintendedpregnancy/usmec.htm). Combined formulations offer contraception, while cyclic progesterone does not. Both offer cyclic withdrawal bleeding. A Cochrane review did not find any RCTs comparing one to the other and therefore either are reasonable options [36].The levonorgestrel IUD is effective at treating AUB as well [31].Women may still experience intermittent vaginal bleeding or amenorrhea so it is less likely to result in cyclic withdrawal bleeding.
All of the above treatments provide the additional benefit of thinning the endometrium and preventing unopposed estrogen effect. This provides further protection the endometrial hyperplasia with chronic anovulatory cycles and unopposed estrogen [31].
In women with PCOS and associated metabolic conditions, first-line treatment is weight loss and other lifestyle interventions to improve or prevent other sequelae of the condition. Weight loss has been shown to reduce circulating androgen levels and increase ovulation. It has been shown to reduce glucose and lipid levels and hirsutism. Pregnancy rates increase as well. Weight loss achieved through medications and gastric bypass has similar effects. There is no special diet that has been shown to be more effective than another [32]. As little as a 5% weight reduction from baseline can improve PCOS symptoms [34,35].
Metformin is also commonly added to lifestyle modifications in women with PCOS to reduce risks for developing diabetes. There is little high quality evidence of added benefit above lifestyle modifications [34].Statin therapy can be considered in women with hyperlipidemia and PCOS [32].
For women with PCOS who desire to conceive, treatment should target increased ovulation. Pre-conception counseling and lifestyle modifications are again first line [32].Ovulation induction interventions carry increased risk of multiple gestation. For ovulation induction, clomiphene citrate is first line therapy. Metformin is commonly used as noted above to improve comorbidities associated with PCOS and can increase ovulation compared to placebo [37].However, RCTs do not support its use as first-line treatment of infertility treatment in PCOS. Clomiphene is 3 times more effective than metformin alone [32].
Medications can improve but often do not resolve hirsutism in women with PCOS. Combined hormonal contraceptives are commonly used off-label and no one type of pill has been shown to be superior. Anti-androgens are also off-label but empirically used. They can also improve lipid and other metabolic variables. They are all teratogenic and therefore should not be used in women who desire conception, and be used with effective contraceptives. Spironolactone is an androgen receptor antagonist. It takes months for effect. Some women will have improved menstrual frequency with this medication as well. Often adjunctive therapy such as eflornithine facial cream or laser therapy or a combination is needed to further treat hirsutism [32,35,38].